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Updated: Jan 12, 2026

Chronic Sleep Deprivation in Mouse Pups by Means of Gentle Handling
Published on: October 11, 2018
Effects of sleep deprivation on cognition and synaptic associated proteins in rodents: A systematic review and
Hongqi Wang1, Xin Mao2, Siyu Liu1
1Department of Anatomy, Beijing Key Laboratory of Neural Regeneration and Repair, School of Basic Medical Sciences, Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
Background:
Sleep disorders are a significant risk factor for cognitive decline and Alzheimer's disease (AD). However, preclinical studies investigating the effects of sleep deprivation (SD) on cognition and synaptic proteins have produced inconsistent findings, hindering translational progress.
Objective:
This systematic review and meta-analysis identify key factors moderating the effects of SD on cognition and synaptic proteins in rodent models.
Methods:
Following PRISMA guidelines, we analyzed 21 eligible studies using meta-analysis, subgroup, meta-regression, and multilevel analyses to identify sources of experimental heterogeneity.
Results:
SD significantly reduced synaptic proteins overall. While the global effect on cognition was not significant, subgroup analyses revealed robust cognitive impairment in Wistar rats undergoing fragmented sleep, particularly when assessed by Morris water maze or novel object recognition tests. Key synaptic proteins (PSD-95, synaptophysin) were consistently reduced in the hippocampus and prefrontal cortex.
Conclusions:
Our comprehensive review synthesizes diverse studies, concluding that methodological choices are the primary drivers of heterogeneity in preclinical SD research. We provide evidence-based guidance for selecting appropriate rodent models, behavioral paradigms, and biochemical indicators to investigate the molecular mechanisms linking sleep disorders and cognitive decline. This work offers a significant framework to standardize and enhance the reliability of preclinical studies. By validating models that directly connect fragmented sleep-a condition common in AD patients-to synaptic pathology in vulnerable brain regions, our research strengthens the mechanistic link between sleep disturbance and cognitive impairment in AD and encourages a greater focus on this critical relationship for the readers of the Journal of Alzheimer's Disease Reports and AD researchers.
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